mt_monashmedfandomcom-20200213-history
L0301P49 - How Cells Communicate
Key Points *cells interact (communicate) with each other during development and in adulthood **cells don’t live in isolation **they are frequently communicating/signalling/“talking” with one another *communication signals regulate the most fundamental processes of cell biology **cell survival **cell division (mitosis) **cell differentiation **cell migration *different types of cell communication **contact-dependent signalling **paracrine signalling **synapses **hormonal (endocrine) signalling *for normal development and adult health cells must: **receive the correct signals **at the correct time **in the correct place **in the correct concentration *not all cells respond to the same signal in the same way *large families of paracrine factors are used repeatedly throughout life (before/after birth) and throughout the animal kingdom, e.g.: **fibroblast growth factors (FGFs) **Wnt family **members of the transforming growth factor-β (TGF-β) family Cell Communication in Foetal Development General Principles *communication between cells is mediated mainly by extracellular signalling molecules **long and short distance signalling **most cells both emit and receive signals *involves more than just the transmission of chemical signals from one cell to another *reception of signals usually requires receptor proteins at the cell surface which bind the signal molecule *the binding activates the receptor/s, which in turn activates one or more intracellular signalling pathways which **process the signal inside the receiving cell **distribute the signal to the appropriate intracellular targets *these targets are generally effector proteins which implement the appropriate change of cell behaviour   *depending on the signal and the nature and state of the receiving cell, these effectors can be **gene regulatory proteins **ion channels **components of a metabolic pathway **parts of the cytoskeleton *mechanisms are required **to control which signals are emitted and when **to enable the signal-receiving cell to interpret the signals Signalling Molecules *includes: **proteins **small peptides **amino acids **nucleotides **steroids **retinoids **fatty acid derivatives **dissolved gasses *highly potent - typically acts at extremely low concentrations (<10-8M) Classification of Signalling Molecules Signal Speed *extracellular signals can act rapidly or slowly to change behaviour of the target cell *fast responses **include changes in cell movement, secretion, metabolism **does not necessarily change gene transcription **may involve rapid phosphorylation of effector proteins *slow responses **include increased cell growth and division **involves changes in gene expression Signal Response *different cell types can respond differently to the same signal *e.g.: acetylcholine **heart muscle - decrease rate and force of concentration **skeletal muscle - increased contraction **salivary gland - secretion Signalling Molecule Receptor Type *regardless of signal type, target cells respond by means of receptors **cell surface receptor **intracellular receptors Intercellular Signalling Endrocine *hormone secreted form endocrine cell *long distance - travels along blood stream until it reaches their target cells *binds to receptor on the target cell and initiates a response Synaptic *neurotransmitters **released from terminal of a neuron **bind to receptors on target cell or post-synaptic terminal to initiate a response Contact-Dependent *signalling molecule remains bound to surface of the signalling cell and binds to receptor on target cell to initiate a response *only influences the cells that contact it *very important in development *communicating cells may send long cytoplasmic processes to contact each other Paracrine *most common type of signalling *local-signalling *secreted into ECF and acts in the local environment (within a few cell diameters) *may cause enzyme coupling **signal molecule is a dimer and joins two catalytic domains to activate it *for local activity, secreted molecules must not be allowed to diffuse too far: **rapidly taken up by target cell **destroyed by extracellular enzymes **immobilised by the ECM (bind to proteoglycans) **activity blocked by secreted protein antagonists Signalling in Development *embryo uses many of the same paracrine factors to construct all tissues and organs Neighbouring Cells *considering signalling molecule concentration, those closest to the inductive cell would receive the greatest signal Patterning and Positional Information *during development, the location of a cell or tissue relative to other cells within the organism influences how that cell will divide and differentiate *due to the fact that growth/paracrine factors (morphogens) diffuse between cells which may respond differently depending on the concentration of the morphogen Paracrine Signalling Molecules Major Families Names do not have anything to do with function *fibroblast growth factor family (FGFs) *Hedgehog family *Wingless family (Wnts) *transforming growth factor-β superfamily (TGF-βs) Example 1: FGF8 (Tyrosine Kinase) *involved in development of many, highly different organs including: **limbs, eye, brain Example 2: BMP4 *Bone Morphogenic Protein 4 *was first discovered to play a role in bone development *more recently discovered to be essential to kidney development *if mutations occur in BMP4, causing too high or too low concentrations: **severe urinary tract abnormalities occur and will lead to renal failure if not treated